N-[2-[(2S,4R)-4-azido-2-cyanopyrrolidin-1-yl]-2-oxoethyl]naphthalene-1-carboxamide | 1374770-18-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[2-[(2S,4R)-4-azido-2-cyanopyrrolidin-1-yl]-2-oxoethyl]naphthalene-1-carboxamide
• CAS: 1374770-18-9
• 化学式: C₁₈H₁₆N₆O₂
• 分子量: 348.364
• InChiKey: IPKHAZSRZNIQAI-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  87.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 吡啶 、 三氟乙酸 作用下， 生成 N-[2-[(2S,4R)-4-azido-2-cyanopyrrolidin-1-yl]-2-oxoethyl]naphthalene-1-carboxamide
  参考文献：
  名称：

  Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity

  摘要：

  A series of N-acylated glycyl-(2-cyano) pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.107

文献信息

• Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity
  作者：Oxana Ryabtsova、Koen Jansen、Sebastiaan Van Goethem、Jurgen Joossens、Jonathan D. Cheng、Anne-Marie Lambeir、Ingrid De Meester、Koen Augustyns、Pieter Van der Veken

  DOI：10.1016/j.bmcl.2012.03.107

  日期：2012.5

  A series of N-acylated glycyl-(2-cyano) pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery. (C) 2012 Elsevier Ltd. All rights reserved.